The publications and other materials used herein to illuminate the background of the invention, and in particular, cases to provide additional details respecting the practice, are incorporated by reference.
Neuropeptide Y (NPY) is a member of the pancreatic polypeptide family and neuromodulator that is secreted widely by neurons of the central and peripheral nervous systems and it is the most abundant peptide in the brain and in the heart (1-4). NPY is the most potent orexigenic neuropeptide and may have tonic inhibitory action on leptin mediated satiety signal (2-3, 5). NPY stimulates insulin secretion (6) and insulin-induced glucose uptake in normal rate (7). In contrast, insulin and insulin-like growth factor II suppress hypothalamic NPY release (8). In animal models of obesity and Type 2 diabetes, enhanced activity of NPY neurons due to hypothalamic resistance of insulin inhibition may contribute to hyperphagia, reduced energy expenditure and obesity (9). Further, NPY participates in the control on hypothalamic-pituitary-adrenal axis (10). In the cardiovascular system NPY is a vasoconstrictor, it inhibits the release of norepinephrine and potentiates the norepinephrine response (11). Interestingly, in experimental diabetes cardiorespiratory responses to NPY have been shown to be altered (12-13). Further, NPY may have angiogenic properties (4) that could enhance the development of atherosclerosis. The widespread effects of NPY are mediated by several different subtypes of NPY receptors (14). We identified a rather common leucine7 to proline7 polymorphism (Leu7/Pro) very recently (15). This polymorphism was found to be associated with significantly higher serum total- and LDL cholesterol levels particularly in obese subjects in two independent Finnish and one Dutch study population. Further, apolipoprotein B levels were elevated in non-diabetic subjects with Leu7/Pro-polymorphism in one of these populations (15). Although the biochemical and physiological link between cholesterol metabolism and NPY is currently not known, the Leu7/Pro-polymorphism of NPY gene should be considered as a new genetic marker for high cholesterol levels in obese subjects.